Interactions between cancer cells and host tissues play an important role in determining the clinical course of cancer. A breakdown in the recognition processes by which cells distinguish self from non-self probably occurs in the change from normal to malignant state and in the spread of cancer by metastasis. We have already shown that the inhibition of the aggregation of embryonic chick neural retina cells by cancer cells serves as a sensitive model system for investigation of cellular recognition in normal-normal and normal-cancer cell interactions using mouse and human cell lines and colon adenocarcinoma tissue. We have also demonstrated that the inhibition is manifest in the inhibition of adhesion of cells. One objective of this project is to study the mechanism of inhibition using the aggregation and adhesion assays in combination. The short-duration adhesion assay will be used to study the effects of modifiers of the cell surface, cell adhesion and cell metabolism on this inhibition. The longer duration of aggregation experiments make it less sensitive to serum-masked, or reversible changes in these properties. Another objective is to study the sensitivity of this system with other human cancers and cell lines with specific behavioral characteristics such as revertant transformed cells or cells of varying metastatic potential or different adhesive behavior. We shall also study in parallel experiments the mechanism of action of cell-free conditioned medium from cancer cells. Our technique involves observing the effects of small numbers of "test" cells on the aggregation or adhesion of neural retina cells. The results are assayed by measuring aggregate diameters or counting numbers of cells adherent to cellular or artificial substrates. Time lapse photomicroscopy will be used to study the behavior of individual cells in stationary culture. We will confirm results obtained with cells suspension using intact cancer and normal tissue fragments to support in vivo applicability of results. The results obtained should add to the understanding of the differential effects of normal and cancer cells on other cell types and may suggest methods of altering cancer cells useful in the clinical treatment of cancer.